title: Effects of the delta-opioid agonist SNC80 on the abuse liability of methadone in rhesus monkeys: a behavioral economic analysis.
abstract: BACKGROUND
  Delta-opioid agonists enhance the antinociceptive efficacy of methadone and other mu-opioid agonists. However, relatively little is known about the degree to which delta agonists might enhance the abuse-related effects of mu agonists.
  
  
  OBJECTIVE
  This study used a behavioral economic approach to examine effects of the delta agonist SNC80 [(+)-4-[(αR)-α-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N,N-diethylbenzamide] on the reinforcing effects of methadone in a drug self-administration assay. Interactions between SNC80 and cocaine were also examined for comparison.
  
  
  METHODS
  Rhesus monkeys (n = 4), surgically implanted with indwelling intravenous catheters, were tested in two phases. In phase 1, drug self-administration dose-effect curves for methadone (0.0032-0.1 mg/kg/injection (inj)) and cocaine (0.0032-0.32 mg/kg/inj) alone were determined under a fixed-ratio 10 (FR 10) schedule of reinforcement. In phase 2, FR values were increased every 3 days (FR 1-FR 1800) during availability of methadone alone (0.032 mg/kg/inj) and in combination with varying proportions of SNC80 (0.1:1, 0.3:1, and 0.9:1 SNC80/methadone) or of cocaine alone (0.032 mg/kg/inj) and in combination with varying proportions of SNC80 (0.33:1, 1:1, and 3:1 SNC80/cocaine). Demand curves related drug intake to FR price, and measures of reinforcement were derived.
  
  
  RESULTS
  Methadone and cocaine alone each functioned as a reinforcer. SNC80 did not alter measures of reinforcement for either methadone or cocaine.
  
  
  CONCLUSIONS
  SNC80 at proportions previously shown to enhance methadone-induced antinociception did not enhance the abuse-related effects of methadone. These results support the proposition that delta agonists may selectively enhance mu agonist analgesic effects without enhancing mu agonist abuse liability.
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, 410 North 12th Street, Richmond, VA 23298, USA.
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Banks
authors.forename: Peter G
authors.initials: PG
authors.lastname: Roma
authors.forename: John E
authors.initials: JE
authors.lastname: Folk
authors.forename: Kenner C
authors.initials: KC
authors.lastname: Rice
authors.forename: S Stevens
authors.initials: SS
authors.lastname: Negus
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001549:Benzamides / Q000008:administration & dosage / Q000494:pharmacology*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008253:Macaca mulatta; D008297:Male; D008691:Methadone / Q000008:administration & dosage / Q000494:pharmacology*; D009293:Opioid-Related Disorders / Q000209:etiology* / Q000378:metabolism / Q000523:psychology; D010146:Pain / Q000523:psychology; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D001549:Benzamides; D010879:Piperazines; D017465:Receptors, Opioid, delta; D017450:Receptors, Opioid, mu; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D003042:Cocaine; D008691:Methadone